Indian Pediatrics

, Volume 47, Issue 1, pp 67–73 | Cite as

Intermittent or daily short course chemotherapy for tuberculosis in children: Meta-analysis of randomized controlled trials

  • P. Ramesh Menon
  • R. Lodha
  • S. Sivanandan
  • S. K. Kabra
Research Paper



To compare the effectiveness of intermittent with daily chemotherapy (both containing rifampicin) in childhood tuberculosis (age ≤16yrs) in achieving cure/significant improvement.


Systematic Review and Meta-analysis.


MEDLINE and the Cochrane Library were searched for randomized trials of antitubercular regimens containing rifampicin, in children 16 yrs or less with tuberculosis. Two reviewers independently assessed trial eligibility and quality. Data from full articles of selected studies were independently extracted by two authors and analyzed. The odds ratio was obtained for the pooled data in two groups (intermittent and daily therapy).

Outcome variables

Cure/significant improvement, relapse rate and adverse events.


Four randomized controlled trials comparing twice weekly and daily therapy including 466 children pulmonary 439; extrapulmonary 27) met the inclusion criteria. Baseline data were comparable. On quality assessment, 3 studies scored 2 and one study scored 3 out of 5 points. Per protocol analysis showed that children receiving intermittent regimen were less likely to be cured than those receiving daily therapy (OR 0.27; 95% CI: 0.14, 0.51). The results of intention to treat analysis suggest similar trend towards lower cure rates with twice weekly regimen (OR 0.66; 95% CI: 0.23–1.84).


Twice weekly intermittent short course therapy is less likely to cure tuberculosis in children as compared to daily therapy. There is a need for better quality randomized controlled trials for assessing efficacy of alternate schedule for intermittent therapy for childhood tuberculosis.

Key words

Children Intermittent therapy Short Course chemotherapy Treatment Tuberculosis 


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  1. 1.
    Cohn DL, Catlin BJ, Peterson KL, Judson FN, Sbarbaro JA. A 62-dose, 6-month therapy for pulmonary and extrapulmonary tuberculosis. A twice-weekly, directly observed and cost-effective regimen. Ann Intern Med 1990;112:407–415.PubMedGoogle Scholar
  2. 2.
    Caminero JA, Pavón JM, Rodríguez de Castro F, Díaz F, Julià G, Caylá JA, et al. Evaluation of a directly observed six month fully intermittent treatment regimens for tuberculosis in patients suspected of poor compliance. Thorax 1996;51:1130–1133.CrossRefPubMedGoogle Scholar
  3. 3.
    Balasubramanian R. Fully intermittent six month regimens for pulmonary tuberculosis in south India. Indian J Tuberc 1991;38:51.Google Scholar
  4. 4.
    Bechan S, Connolly C, Short GM, Standing E, Wilkinson D. Directly observed therapy for tuberculosis given twice weekly in the workplace in urban South Africa. Trans Royal Soc Trop Med Hyg 1997;91:704–707.CrossRefGoogle Scholar
  5. 5.
    CDC core curriculum: treatment of TB Disease. Accessed on 12 December, 2007.
  6. 6.
    Abernathy RS, Dutt AK, Stead WW, Moers DJ. Short-course chemotherapy for tuberculosis in children. Pediatrics 1983;72:801–806.PubMedGoogle Scholar
  7. 7.
    Iseman MD, Cohn DL, Sbarbaro JA. Directly observed treatment of tuberculosis — we can’t afford not to try it. N Engl J Med 1993;328:576–578.CrossRefPubMedGoogle Scholar
  8. 8.
    Dickersin K, Scherer R, Lefebvre C. Systematic reviews: Identifying relevant studies for systematic reviews. BMJ 1994;309:1286–1291.PubMedGoogle Scholar
  9. 9.
    Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJ, Gavaghan DJ, et al. Assessing the quality of reports of Randomized clinical trials: is blinding necessary? Controlled Clin Trials 1996;17:1–12.CrossRefPubMedGoogle Scholar
  10. 10.
    RevMan Analyses [Computer program]. In: Review Manager (RevMan). Version 4.2 for Windows. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration; 2003.Google Scholar
  11. 11.
    Dingley HB. Short-term chemotherapy in tuberculosis in children. Indian J Tuberc 1982;29:48–54.Google Scholar
  12. 12.
    Jawahar MS, Rajaram K, Sivasubramanian S, Paramasivan CN, Chandrasekar K, Kamaludeen MN, et al. Treatment of lymph node tuberculosis—a randomized clinical trial of two 6-month regimens. Trop Med Int Health 2005;10:1090–1098.CrossRefPubMedGoogle Scholar
  13. 13.
    Rajeswari R, Sivasubramanian S, Balambal R, Parthasarathy R, Ranjani R, Santha T, et al. A controlled clinical trial of short-course chemotherapy for tuberculoma of the brain. Tuber Lung Dis 1995;76:311–317.CrossRefPubMedGoogle Scholar
  14. 14.
    Balasubramanian R, Nagarajan M, Balambal R, Tripathy SP, Sundararaman R, Venkatesan P, et al. Randomised controlled clinical trial of short course chemotherapy in abdominal tuberculosis: a five-year report. Int J Tuberc Lung Dis 1997;1:44–51.PubMedGoogle Scholar
  15. 15.
    Anonymous. Controlled clinical trial of oral short-course regimens in the treatment of sputum-positive pulmonary tuberculosis. Tuberculosis Research Centre. Int J Tuberc Lung Dis 1997;1:509–517.Google Scholar
  16. 16.
    Swaminathan S, Raghavan A, Duraipandian M, Kripasankar AS, Ramachandran P. Short course chemotherapy for pediatric respiratory tuberculosis: 5-year report. Int J Tuberc Lung Dis 2005;9:693–696.PubMedGoogle Scholar
  17. 17.
    Ramachandran P, Kripasankar AS, Duraipandian M. Short Course Chemotherapy for pulmonary tuberculosis in children. Indian J Tuberc 1998;45:83–87.Google Scholar
  18. 18.
    Kansoy S, Kurtap N, Akpit S, Aksoylar S, Yaprak I, Çaðlayan S. Superiority of intermittent-short course chemotherapy in childhood pulmonary tuberculosis. Turkish J Med Sci 1996;26:41–43.Google Scholar
  19. 19.
    Kumar L, Dhand R, Singhi PD, Rao KL, Katariya S. A randomised trial of fully intermittent and daily followed by intermittent short-course chemotherapy for childhood tuberculosis. Pediatr Infect Dis J 1990;9:802–806.PubMedCrossRefGoogle Scholar
  20. 20.
    Te Water Naude JM, Donald PR, Hussey GD, Kibel MA, Louw A, Perkins DR, et al. Twiceweekly vs daily chemotherapy for childhood TB. Pediatr Infect Dis J 2000;19:405–410.CrossRefGoogle Scholar
  21. 21.
    World Health Organization. Provisional guidelines for the diagnosis and classification of the EPI target diseases for primary health care, surveillance and special studies. EPI/GEN/83/4. Geneva: WHO; 1983.Google Scholar
  22. 22.
    Mwandumba HC, Squire SB. Fully intermittent dosing with drugs for treating tuberculosis in adults. Cochrane Database Syst Rev 2001;4:CD000970.PubMedGoogle Scholar
  23. 23.
    Cox HS, Morrow M, Deutschmann PW. Long term efficacy of DOTS regimens for tuberculosis: systematic review. BMJ 2008;336:484–487.CrossRefPubMedGoogle Scholar
  24. 24.
    Walley JD, Khan MA, Newell JN, Khan MH. Effectiveness of the direct observation component of DOTS for tuberculosis: a randomized controlled trial in Pakistan. Lancet 2001;357:664–669.CrossRefPubMedGoogle Scholar
  25. 25.
    Snider DE, Graczyk J, Bek E, Rogowski J. Supervised six-months treatment of newly diagnosed pulmonary tuberculosis using isoniazid, rifampin, and pyrazinamide with and without streptomycin. Am Rev Respir Dis 1984;130:1091–1094.PubMedGoogle Scholar

Copyright information

© Indian Academy of Pediatrics 2010

Authors and Affiliations

  • P. Ramesh Menon
    • 1
  • R. Lodha
    • 1
  • S. Sivanandan
    • 1
  • S. K. Kabra
    • 1
  1. 1.Department of PediatricsAll India Institute of Medical SciencesNew DelhiIndia

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